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PubMed2004

Absence of mutations in the Wilms' tumor gene wt1 in de novo non-small cell lung cancers.

We recently demonstrated that the WT1 gene was overexpressed in the majority of de novo lung cancers regardless of cancer subtypes. Here, we examined WT1 genomic DNA in 38 cases of de novo non-small cell lung cancers (NSCLC) for mutations using direct sequencing. The sequencing analysis showed no mutations of WT1 genomic DNA in any of 38 de novo non-small cell lung cancers examined. These results indicated that the non-mutated, wild-type WT1 gene played an important role in de novo NSCLC.

Adult↗

PubMed2005

[Oligonucleotide microarray for human immunodeficiency virus detection].

OBJECTIVE: To develop an oligonucleotide microarray for fast detection of human immunodeficiency virus (HIV). METHODS: With complete genome sequence of HIV-1 subtype B (U26942) as the target sequence and bioinformatics software such as DNAClub, Oligo6.0, BLAST, Alignment, oligonucleotide probes of high specificity with identical length and similar melting temperature (T(m)) were designed and synthesized. Oligonucleotide microarray was prepared using Cartesian Microarrayer. Using the plasmids of HIV-1 subtype B(U26942), C(U46016), F(AF075703), G(AF061640) and restriction display technique, Cy3-labeled HIV DNA fragments were amplified and the hybridization results were scanned and analyzed with Array-Pro. RESULTS AND CONCLUSION: Twenty-two optimized oligonucleotide microarray probes were obtained and used to prepare the oligonucleotide microarray for further screening studies. The microarray prepared significantly enhanced the sensitivity, reliability and speed of DNA assay, and possesses the potential for application in clinical setting.

Base Sequence↗

PubMed1999

Long terminal repeat promoter/enhancer activity of different subtypes of HIV type 1.

Transcription of the HIV-1 provirus genome is regulated by a complex interplay between viral regulatory proteins and cellular transcription factors that interact with the viral long terminal repeat (LTR) region of HIV-1. However, several cellular transcription factors have been identified that can interact with the HIV-1 LTR; the significance of all of these factors is not clearly understood. In this study we have characterized the LTR region of different subtypes of HIV-1 with regard to nucleotide sequence and promoter activity. The LTR regions of HIV-1 from peripheral blood mononuclear cells of 29 infected individuals originating from 10 different geographical regions were sequenced and further analyzed for promoter/enhancer activity in transient transfection of HeLa cells, in the context of a reporter gene and in the context of the complete virus genome. We found several subtype-specific LTR sequences of the various HIV-1 strains, such as an insertion that created a potential third NF-kappaB site in the LTR of the subtype C strains. The USF-binding site in the NRE also contained subtype-specific sequences. Interestingly, the promoter/enhancer activities of the subtype C LTRs were higher than the activities of the other subtypes analyzed here (subtypes A, B, D, E, and G), suggesting that the potential third NF-kappaB site may confer higher LTR activity or that the subtype C NRE may be less potent. Thus, our data suggest that genetic diversity of the LTR may result in HIV-1 subtypes with different replicative properties.

Adult↗

PubMedDate not supplied

[Primary structure of the hemagglutinin gene in strains of the influenza virus A/Leningrad/624/86 and A/Leningrad/621/86 serologic subtype H1N1].

A molecular analysis was made of genomes of influenza A (H1N1) virus strains, the causative agents of an epidemic in Leningrad, 1986. The primary structure of hemagglutinin gene of two of these strains, A/Leningrad/624/86 and A/Leningrad/621/86, was established, as well as partial primary structure of PB1 gene of certain current strains of the A (H1N1) subtype. A hypothesis of a "shift" of PB1 gene in 1950-1957 is suggested.

Base Sequence↗

PubMed1995

Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype.

The melanocortin (MC) peptides mediate a diverse spectrum of biological activities in both the central nervous system and peripheral tissues by interacting with specific guanine nucleotide binding (G protein)-coupled receptors. Previously, four human melanocortin receptor subtypes have been cloned and characterized. In this study, we have isolated mouse complementary DNA (cDNA) and human genomic clones encoding a fifth melanocortin receptor subtype, MC5. Melanocortin peptide stimulation of human MC5, transiently expressed in COS1 cells, results in activation of adenylate cyclase with the following rank order of potency: [Nle4, D-Phe7]-alpha-MSH (melanocyte stimulating hormone) > ACTH (1-24) (adrenocorticotropic hormone) > alpha-MSH > beta-MSH > gamma-MSH. Northern blot hybridization, ribonuclease protection, and reverse transcription/polymerase chain reaction assays indicate that mouse MC5 mRNA is most abundant in skeletal muscle and brain. Lower but detectable levels of MC5 mRNA are also found in RT2-2 retinal neuronal cells, lung, testis, spleen, heart, kidney, and liver.

Amino Acid Sequence↗

PubMed1997

Primary infections with HIV-1 of women and their offspring in Rwanda: findings of heterogeneity at seroconversion, coinfection, and recombinants of HIV-1 subtypes A and C.

Variation in HIV-1 genomic RNA was studied in seroconversion samples from mother-child pairs from a Rwandan cohort. The mothers (n = 8) were heterosexually infected and their children (n = 6) were vertically infected by breast milk. Five of the children seroconverted within the same 3-month period as did their mothers. Highly homogeneous subtype A V3 and p17gag sequence populations were observed in three mother-child pairs, one of the two nontransmitting mothers, and one child (mean nucleotide distances 0 to 0.9%). Heterogeneous populations of subtype A V3 and p17gag sequences were found in one mother and a mother-child pair (1.4 to 2.8% for V3, 1.0 to 1.9% for p17). The second nontransmitting mother was infected with a heterogeneous AV1-V3/Cp17-p24 recombinant virus population (3. 8% for V3, 2.4% for p17). Finally, in one woman subtype C V3 sequences were observed, in addition to highly homogeneous subtype A V3 and p17gag sequence populations, also found in the child. Coexistence of subtype AV1-V3 and CV1-V3 env sequences in the mother was confirmed in a follow-up sample. The gag gene of both the maternal and the child's virus population represented an A/C recombinant sequence (Ap17/Cp24). An infection with subtype CV1-V3/p17-p24 was found upon testing of three additional participants of the mother-child cohort, indicating that subtype C is present in Rwanda. In conclusion, heterogeneity, coinfection, and intersubtype recombinants are not uncommon in primary HIV-1 infections in Rwanda.

Amino Acid Sequence↗

PubMed1998

An isolate of human immunodeficiency virus type 1 originally classified as subtype I represents a complex mosaic comprising three different group M subtypes (A, G, and I).

Full-length reference clones and sequences are currently available for eight human immunodeficiency virus type 1 (HIV-1) group M subtypes (A through H), but none have been reported for subtypes I and J, which have only been identified in a few individuals. Phylogenetic information for subtype I, in particular, is limited since only about 400 bp of env gene sequences have been determined for just two epidemiologically linked viruses infecting a couple who were heterosexual intravenous drug users from Cyprus. To characterize subtype I in greater detail, we employed long-range PCR to clone a full-length provirus (94CY032.3) from an isolate obtained from one of the individuals originally reported to be infected with this subtype. Phylogenetic analysis of C2-V3 env gene sequences confirmed that 94CY032.3 was closely related to sequences previously classified as subtype I. However, analysis of the remainder of its genome revealed various regions in which 94CY032.3 was significantly clustered with either subtype A or subtype G. Only sequences located in vpr and nef, as well as the middle portions of pol and env, formed independent lineages roughly equidistant from all other known subtypes. Since these latter regions most likely have a common origin, we classify them all as subtype I. These results thus indicate that the originally reported prototypic subtype I isolate 94CY032 represents a triple recombinant (A/G/I) with at least 11 points of recombination crossover. We also screened HIV-1 recombinants with regions of uncertain subtype assignment for the presence of subtype I sequences. This analysis revealed that two of the earliest mosaics from Africa, Z321B (A/G/?) and MAL (A/D/?), contain short segments of sequence which clustered closely with the subtype I domains of 94CY032.3. Since Z321 was isolated in 1976, subtype I as well as subtypes A and G must have existed in Central Africa prior to that date. The discovery of subtype I in HIV-1 hybrids from widely distant geographic locations also suggests a more widespread distribution of this virus subtype, or at least segments of it, than previously recognized.

Base Sequence↗

PubMed2005

Genomic gains and losses influence expression levels of genes located within the affected regions: a study on acute myeloid leukemias with trisomy 8, 11, or 13, monosomy 7, or deletion 5q.

We performed microarray analyses in AML with trisomies 8 (n=12), 11 (n=7), 13 (n=7), monosomy 7 (n=9), and deletion 5q (n=7) as sole changes to investigate whether genomic gains and losses translate into altered expression levels of genes located in the affected chromosomal regions. Controls were 104 AML with normal karyotype. In subgroups with trisomy, the median expression of genes located on gained chromosomes was higher, while in AML with monosomy 7 and deletion 5q the median expression of genes located in deleted regions was lower. The 50 most differentially expressed genes, as compared to all other subtypes, were equally distributed over the genome in AML subgroups with trisomies. In contrast, 30 and 86% of the most differentially expressed genes characteristic for AML with 5q deletion and monosomy 7 are located on chromosomes 5 or 7. In conclusion, gain of whole chromosomes leads to overexpression of genes located on the respective chromosomes. Losses of larger regions of the genome translate into lower expression of the majority of genes represented by only one allele. The reduced expression of these genes is the most characteristic difference in gene expression profiles between AML with monosomy 7 and AML with deletion 5q, respectively, and other AML subtypes. Therefore, these data provide evidence that gene dosage effects gene expression in AML with unbalanced karyotype abnormalities. Losses of specific regions of the genome determine the gene expression profile more strongly than the gain of whole chromosomes.

Chromosome Aberrations↗

PubMed2004

Characterization of the murine alpha interferon gene family.

Mouse and human genomes carry more than a dozen genes coding for closely related alpha interferon (IFN-alpha) subtypes. IFN-alpha, as well as IFN-beta, IFN-kappa, IFN-epsilon, and limitin, are thought to bind the same receptor, raising the question of whether different IFN subtypes possess specific functions. As some confusion existed in the identity and characteristics of mouse IFN-alpha subtypes, the availability of data from the mouse genome sequence prompted us to characterize the murine IFN-alpha family. A total of 14 IFN-alpha genes were detected in the mouse genome, in addition to three IFN-alpha pseudogenes. Four IFN-alpha genes (IFN-alpha1, IFN-alpha7/10, IFN-alpha8/6, and IFN-alpha11) exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN-alpha subtypes were found to be stable at pH 2 and to exhibit antiviral activity. Interestingly, some IFN subtypes (IFN-alpha4, IFN-alpha11, IFN-alpha12, IFN-beta, and limitin) showed higher biological activity levels than others, whereas IFN-alpha7/10 exhibited lower activity. Most murine IFN-alpha turned out to be N-glycosylated. However, no correlation was found between N-glycosylation and activity. The various IFN-alpha subtypes displayed a good correlation between their antiviral and antiproliferative potencies, suggesting that IFN-alpha subtypes did not diverge primarily to acquire specific biological activities but probably evolved to acquire specific expression patterns. In L929 cells, IFN genes activated in response to poly(I*C) transfection or to viral infection were, however, similar.

Alleles↗

PubMed2000

Full-genome nucleotide sequence of a hepatitis C virus variant (isolate name VAT96) representing a new subtype within the genotype 2 (arbitrarily 2k).

Hepatitis C virus (HCV), a single-stranded RNA virus of the family Flaviviridae, has a wide range of genetic heterogeneity: 6-11 genotypes (or 6 clades) have been known and each genotype comprises multiple subtypes. Here we report the entire nucleotide sequence of an HCV isolate from a patient in Moldova with chronic hepatitis (isolate name VAT96). The genetic organization of VAT96 was, from 5' to 3' ends, 5'UTR (341 nt), polyprotein ORF (9099 nt), 3'UTR (38 nt except for the poly-U and poly-pyrimidine stretch), and X-tail (98 nt). Comparison of the polyprotein amino acid sequence of VAT96 with those of known full-genome isolates assigned VAT96 to the genotype 2 (or clade 2), and further phylogenetic analysis based on a 447-nt sequence that covers part of the C and El regions suggested that VAT96 represents a new subtype within the genotype 2, arbitrarily designated "2k" VAT96 was unique in that it possessed a U residue prior to GCC at the 5' end of its genome while all the other full-genome HCV sequences start with GCC or ACC. In addition, the polyprotein ORF of HCV-VAT96, like HCV-BEBE1 of 2c, encoded several additional amino acids in excess, compared to 2a and 2b sequences. Despite these characteristics that may be unique to VAT96, the 98-nt sequence of the X-tail of VAT96 was highly homologous to those of other isolates with different genotypes so far reported.

3' Untranslated Regions↗

PubMed2026

The Landmark Series: Mutation-Based Therapy of Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited long-term survival despite advances in surgery and systemic therapy. PATIENTS: The population of interest comprises patients with PDAC characterized by targetable molecular alterations and biologically distinct transcriptomic subtypes. METHODS: We performed a narrative review of landmark and contemporary clinical trials, translational studies, and emerging molecular-classification platforms relevant to precision oncology in PDAC. RESULTS: Growing understanding of PDAC molecular biology has identified putative genetic mutations, including homologous recombination repair deficiency, mismatch repair deficiency, and mutated KRAS, enabling the development of targeted therapies and precision treatment strategies. Concurrently, transcriptomic profiling has revealed biologically distinct molecular subtypes associated with differences in prognosis and therapeutic response. Emerging tools such as molecular classifiers, deep learning models, and multiomic platforms may further refine patient selection and treatment personalization. CONCLUSIONS: This review highlights contemporary efforts of novel targeted therapies, ongoing advances in molecular subtyping, and the evolving role of precision oncology in improving outcomes for patients with PDAC.

Genomic alterations↗

PubMed2006

Genomic alterations in ectopic and eutopic endometria of women with endometriosis.

BACKGROUND/AIMS: Ectopic and eutopic endometria of women with endometriosis have been shown to contain genomic alterations. In this study, we sought to identify genomic alterations in both ectopic and eutopic endometria of 5 women with endometriosis and to examine whether the two tissues share any genomic alterations. We also attempted to classify tissue samples based on the alteration profiles. METHODS: Laser capture microdissection was used to harvest epithelial cells. High-resolution comparative genomic hybridization microarrays were used to identify genomic alterations in eutopic and ectopic endometria from 5 women with endometriosis. The results were validated by real-time RT-PCR and loss of heterozygosity analysis. RESULTS: All 5 patients had genomic alterations in their eutopic and ectopic endometria. The ectopic and eutopic endometria shared a sizable portion of genomic alterations. Cluster analysis of the genomic alteration profile correctly and consistently classified tissue samples from the 5 patients into two groups: peritoneal implants and ovarian cysts. CONCLUSIONS: The correct classification of tissue samples into two groups suggests that these two subtypes of endometriosis may have distinct genomic alteration profiles and are thus distinct entities, as previously proposed. The shared alterations are likely the ones that harbor genes responsible for an increased propensity of endometrial debris to implant to the ectopic sites and for early events that lead to the establishment of lesions. Alternatively, these shared alterations may harbor genes that are dysregulated in both eutopic and ectopic endometria. The identified genomic alterations should help to zero in genes involved in the pathogenesis of endometriosis in future studies.

Adult↗

PubMed2026

Integration of Genome-Wide Association Studies With Single-Cell and Bulk Expression Quantitative Trait Locus to Identify Stroke Susceptibility Genes.

BACKGROUND: Previous studies have integrated genome-wide association studies with expression quantitative trait locus (eQTL) data from bulk tissues to identify stroke susceptibility genes. However, eQTL data exhibit high cell-type specificity, and genetic variants may have distinct effects across stroke subtypes. METHODS: We applied the summary-data-based Mendelian randomization (MR) method to integrate eQTL data from 7 brain cell types with genome-wide association studies data for 5 stroke phenotypes (stroke, ischemic stroke, cardioembolic stroke, large artery stroke, and small vessel stroke). Results were compared with summary-data-based MR using eQTL data from 49 tissues in the Genotype-Tissue Expression project. Robustness of significant single-cell summary-data-based MR associations was assessed via MR and colocalization analyses. Further evaluations included single-cell RNA-seq differential expression, protein-protein interaction, druggability, and phenome-wide association studies. RESULTS: Single-cell summary-data-based MR identified many novel significant genes not detected using bulk tissue eQTL data. Validated associations revealed 2 stroke risk genes (LRCH1, ICA1L), 3 stroke protective genes (AHI1, LYRM9, CENPQ), 2 large artery stroke risk genes (LIPA, ELL), and 1 ischemic stroke protective gene (CENPQ). Single-cell RNA-seq showed significantly increased LIPA expression in mouse stroke samples compared with controls. Protein-protein interaction and druggability analyses, along with phenome-wide association studies, prioritized LIPA and LRCH1 as potential therapeutic targets for stroke while indicating possible adverse effects. CONCLUSIONS: Integrating single-cell eQTL with stroke-subtype genome-wide association studies uncovers novel cell-type-specific causal genes and highlights promising therapeutic targets, advancing understanding of stroke pathogenesis.

Genome-Wide Association Study↗

PubMed1997

Evolution and probable transmission of intersubtype recombinant human immunodeficiency virus type 1 in a Zambian couple.

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from the introduction of mutations by an error-prone reverse transcriptase and from recombination of the two RNA genomes packaged in the virion during the synthesis of proviral DNA. The occurrence of multiple, genetically distant HIV-1 subtypes and their geographic intermixing set up conditions for dramatic, rather than gradual, changes in genotype whenever genomes from different subtypes are copackaged in virions. Here we describe, for the first time, the sequential generation of multiple different, but related, intersubtype HIV-1 recombinants within an infected individual. Full-length gag and env genes were recovered directly from peripheral blood mononuclear cells or from primary virus cultures, using serial blood samples from a Zambian woman and a sample from her spouse. DNA sequencing and phylogenetic analysis established that two different A/C recombinant forms of HIV-1 predominated at two time points in the woman. A related but distinct recombinant HIV-1 was recovered from her spouse. Intersubtype recombination apparently played a central role in the evolution of HIV-1 in this couple and may contribute substantially to the rapid emergence of HIV-1 variants whenever mixed-subtype HIV-1 infections occur.

Base Sequence↗

PubMed2025

Distinct Clinicogenomic Features and Immunotherapy Associations in Pulmonary Sarcomatoid Carcinoma: A Multicenter Retrospective Study.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a rare NSCLC subtype with poor prognosis. Outcomes to immune checkpoint inhibitors (ICIs) and genomic features in PSC remain underexplored compared with other NSCLC subtypes. METHODS: Patients from three institutions and the National Cancer Database (NCDB) with metastatic NSCLC treated with ICI alone or with chemotherapy were identified. Clinicogenomics and treatment outcomes were compared across PSC, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). RESULTS: We analyzed 4841 patients including 165 PSC cases treated with ICI-based therapy from three institutions and 201 PSC from NCDB. In MDACC, 65 (4.3%) were PSC, 1138 (75.1%) LUAD, and 312 (20.6%) LUSC. Patients with PSC were older and more likely to present with metastatic disease. In both the MDACC and NCDB cohorts, ICIs resulted in better outcomes for patients with PSC compared with chemotherapy. In these patients, there was no difference in outcome between ICI-monotherapy and ICI-chemotherapy. Across the three institutional cohorts, 37% to 43% of patients with PSC who received ICIs were responders, compared with 26% to 29% in LUAD and 22% to 46% in LUSC (p < 0.05). Improved ICI outcomes in PSC appeared driven by high PD-L1 (≥50% in 73%-77% cases). Among patients with high PD-L1, response rates were similar across histologic subtypes. Conversely, TMB was similar in PSC compared with LUAD or LUSC and was not associated with ICI outcomes. Across cohorts, PSC tumors were enriched for TP53, NF1, NF2, and NRAS, with relative depletion of STK11 and KEAP1 compared with LUAD. Case observation revealed relatively better outcomes to ICI than targeted therapies in patients with PSC with MET exon 14 skipping or KRAS G12C. CONCLUSION: PSC exhibits improved outcomes to ICI relative to other therapies, potentially driven by high PD-L1 expression. Genomic analysis highlights a distinct genomic landscape of PSC when compared with LUAD.

Humans↗

PubMed2026

Excitation/inhibition balance subtypes in autism and their genetic, neural, and clinical profiles.

Excitation (E)/inhibition (I) imbalance is considered a key mechanism in Autism Spectrum Disorder (ASD). However, E/I imbalance can have different etiologies with increased E relative to I (E > I) and increased I relative to E (E < I). Both neural profiles can be associated with altered clinical phenotype, suggesting "bell"-shape brain-behavior relationships. We derived E/I balance measures from resting-state EEG in a large sex-balanced sample of youths with and without autism (N = 310; 164 youths with ASD and 146 typically developing (TD) youths) to address group discriminative power of neural markers, their relation to social skills, and the potential to define different neural subtypes within the autistic group. We also conducted genome-wide copy number variant (CNV) and gene expression analyses to provide additional insight into distinct neural subtypes in autism. A high-density 128-channel electroencephalography (EEG) was used to register neural activity of participants, blood samples were collected from the ASD youths to obtain genomic DNA, and rich behavioral phenotyping was provided for each participant. The results revealed three subgroups within the autistic cohort with the presence of "typical" E/I, E > I, and E < I neural profiles. The two subgroups with E/I imbalance had altered clinical phenotypes. In addition, these subgroups had different genetic profiles, showing that genes within identified CNVs had distinct expression patterns with the evidence of more prenatal (E < I) vs. postnatal (E > I) gene expression. The study suggests that the proposed clustering approach has relevance for the identification of clinically meaningful neural and genetic subtypes within a heterogeneous autistic cohort.

Autism spectrum disorder↗

PubMed1996

Full-length sequence of an ethiopian human immunodeficiency virus type 1 (HIV-1) isolate of genetic subtype C.

Genetic subtype C of the human immunodeficiency virus type-1 (HIV-1) has established foci of infection in India and in at least eight African countries, and is expected to contribute significantly to the global pandemic. Here we report the first almost full-length sequence of a subtype C HIV-1 from Ethiopia. Clone C2220, 9031 nt in length, was derived by long PCR amplification of proviral DNA from virus cultured on primary peripheral blood mononuclear cells, and contains all but 74 nt of the unique sequence information of the HIV-1 genome. This clone resembles HIV-1 isolates of subtypes A, B, and D in its genome organization with one notable exception: the core promoter contains not two, but three potential binding sites for the transcription factor NF-kB. The extra NF-kB site was found in all other Ethiopian strains analyzed, as well as in subtype C viruses from Zambia, suggesting it is typical for the C-subtype of HIV-1. The phylogenetic relationship of C2220 to other HIV-1 isolates is also presented. Subtype C viruses circulating in Ethiopia exhibit the low interisolate diversity typical of other, newly established HIV-1 epidemics, and C2220 is both representative of Ethiopian subtype C viruses and a suitable prototype for the development of vaccines against HIV-1 subtype C.

Amino Acid Sequence↗

PubMed1999

Emerging recombinant human immunodeficiency viruses: uneven representation of the envelope V3 region.

OBJECTIVE: To determine whether the envelope V3 region from HIV-1 subtypes A, C or D had the same probability of being present in intersubtype recombinant genomes. MATERIALS AND METHODS: The envelope C2-C5 and the gag p24-p7 regions from one hundred infants infected perinatally in Tanzania were compared using phylogenetic and recombination analysis. Exact binomial and Fisher's exact tests were used to assess if various genomic regions were more likely to be overrepresented in intersubtype recombinants. RESULTS: Of one hundred HIV-1 positive infants analyzed, twenty-two (22%) showed exclusively subtype A sequence in gag and env. Subtype C accounted for twenty-two infants (22%) whereas nineteen infants (19%) were infected by HIV-1 subtype D. Intersubtype recombinant genomes accounted for thirty-seven infections (37%). The V3 region from subtype A was found in all fifteen A-D recombinants (P = 0.00003) and the V3 region from subtype C was found in all twelve C-D recombinants (P = 0.0002). Conversely, subtype D gag sequences were preferentially represented in the gag of A-D recombinants (P = 0.0003) as well as C-D recombinants (P = 0.002). In A-D recombinants, the V3 region of subtype A was generally surrounded by subtype A C3-C5 sequences. In contrast, the V3 region from subtype C was surrounded by subtype D C3-C5 sequences in C-D recombinants. Significant differences were not found in the number of subtype A or subtype C sequences in A-C recombinants. CONCLUSION: We have shown that several recombinant HIV-1 viruses have been generated and efficiently transmitted to infants in Tanzania. The recombination patterns showed that the V3 region of subtypes A or C was always selected in A-D and C-D recombinants. This selection suggests that the fitness of subtype D-V3 in perinatal transmission may be reduced with respect to V3 from subtype A and/or subtype C. The elevated number of recombinants transmitted perinatally suggests that co-infection or super-infection by two HIV-1 subtypes is not uncommon in this population.

Amino Acid Sequence↗